The human body contains a number of glands including the lacrimal and meibomian glands of the eye, the sebaceous or pilo-sebaceous hair glands on the face and underarms, and the mammary glands in the breasts. These glands may malfunction due to age, irritation, environmental conditions, cellular debris, inflammation, hormonal imbalance and other causes. One common disease state of the eyelid glands is the restriction or stoppage of the natural flow of fluid out of the gland caused by an obstruction.
In the human eye, the tear film covering the ocular surfaces is composed of three layers. The innermost layer in contact with the ocular surface is the mucus layer comprised of many mucins. The middle layer comprising the bulk of the tear film is the aqueous layer, and the outermost layer is a thin (less than 250 nanometers (nm)) layer comprised of many lipids known as “meibum” or “sebum.” The sebum is secreted by the meibomian glands, which are enlarged specialized sebaceous-type glands (hence, the use of “sebum” to describe the secretion) located on both the upper and lower eyelids, with orifices designed to discharge the lipid secretions onto the eyelid margins, thus forming the lipid layer of the tear film. The typical upper eyelid has about twenty-five (25) meibomian glands and the lower eyelid has about twenty (20) meibomian glands, which are somewhat larger than those located in the upper eyelid and which therefore contribute a greater amount of these lipid secretions. The meibomian gland comprises various sac-like acini which discharge the secretion into the main central duct of the gland. The secretion then passes into the orifices which are surrounded by smooth muscle tissue and the muscle of Riolan which are presumed to aid in the expression of sebum. The meibomian gland orifices open onto the eyelid margin at and around the junction of the inner mucous membrane and the outer skin of the eyelids' mucocutaneous junction.
Specifically, each meibomian gland has a straight long central duct lined with four (4) epithelial layers on the inner surface of the duct. Along the length of the central duct there are multiple lateral out-pouching structures, termed acini, where the secretion of the gland is manufactured. The inner lining of each acinus differs from the main central duct in that these specialized cells provide the secretions of the meibomian gland. The secretions flow from each acinus to the duct. There appears to be a valve system between each acinus and the central duct to retain the secretion until it is required, at which time it is discharged into the central duct. The meibomian secretion is then stored in the central duct and is released through the orifice of each gland onto the eyelid margin. Blinking and the squeezing action of the muscle of Riolan surrounding the meibomian glands are thought to be the primary mechanisms to open the orifice for the release of secretion from the meibomian gland.
The sebum that forms the outermost lipid layer is secreted by meibomian glands 10 of the eye, as illustrated in FIGS. 1-3. The meibomian glands are enlarged, specialized sebaceous-type glands (hence, the use of “sebum” to describe the secretion) located on both an upper eyelid 12 and a lower eyelid 14. The meibomian glands 10 contain orifices 16 that are designed to discharge lipid secretions onto the eyelid margins, thus forming the lipid layer of the tear film as the mammal blinks and spreads the lipid secretion. The typical human upper eyelid 12 has about twenty five (25) meibomian glands and the lower eyelid 14 has about twenty (20) meibomian glands, which are somewhat larger than those located in the upper eyelid. Each meibomian gland 10 has a straight long channel or central duct 18 lined with four (4) epithelial layers on the inner surface of the central duct 18. The central duct 18 may also be referred to herein as “meibomian gland channel.” Along the length of the central duct 18 are multiple lateral out-pouching structures 20, termed acini, where the secretion of the meibomian gland 10 is manufactured. The inner lining of each acinus 20 differs from the main central duct 18 in that these specialized cells provide the secretions of the meibomian gland 10. The secretions flow from each acinus 20 to the central duct 18.
There appears to be a valve system between each acinus 20 and the central duct 18 to retain the secretion until it is required, at which time it is discharged into the central duct 18. The meibomian secretion is then stored in the central duct 18 and is released through the orifice 16 of each meibomian gland 10 onto the eyelid margin. Blinking and the squeezing action of the muscle of Riolan surrounding the meibomian glands 10 are thought to be the primary mechanism to open the orifice 16 for the release of secretion from the meibomian gland 10. Blinking causes the upper eyelid 12 to pull a sheet of the lipids secreted by the meibomian glands 10 over the other two (2) layers of the tear film, thus forming a type of protective coating which limits the rate at which the underlying layers evaporate. Thus, a defective lipid layer or an insufficient quantity of such lipids can result in accelerated evaporation of the aqueous layer which, in turn, causes symptoms such as itchiness, burning, irritation, and dryness, which are collectively referred to as “dry eye.”
Dry eye states have many etiologies. A common cause of common dry eye states is the condition known as “meibomian gland dysfunction” (MGD), a disorder where the meibomian glands are obstructed or occluded. As employed herein the terms “occluded” and “obstruction” as they relate to meibomian gland dysfunction are defined as partially or completely blocked or plugged meibomian glands, or any component thereof, including a channel or duct, having a solid, semi-solid or thickened congealed secretion and/or plug, leading to a compromise, or more specifically, a decrease or cessation of secretion. Also, with a reduced or limited secretion, the meibomian gland may be compromised by the occluded or obstructive condition as may be evidenced by a yellowish color indicating a possible infection state, or may be otherwise compromised so that the resulting protective lipid protective film is not adequate.
Meibomitis, an inflammation of the meibomian glands leading to their dysfunction, is usually accompanied by blepharitis (inflammation of the eyelids). Meibomian gland dysfunction may accompany meibomitis, or meibomian gland dysfunction may be present without obvious eyelid inflammation. Meibomian gland dysfunction is frequently the result of keratotic obstructions which partially or completely block the meibomian gland orifices and/or the central duct (canal) of the meibomian gland, or possibly the acini or acini valves (assuming they do in fact exist) or the acini's junction with the central duct. Such obstructions compromise the secretory functions of the individual meibomian glands. More particularly, these keratotic obstructions are comprised of bacteria, sebaceous ground substance, or dead and/or desquamated epithelial cells. See Korb et al., “Meibomian Gland Dysfunction and Contact Lens Intolerance,” Journal of the Optometric Association, Vol. 51, Number 3, (1980), pp. 243-251. While meibomitis is obvious by inspection of the external eyelids, meibomian gland dysfunction may not be obvious even when examined with the magnification of a slit-lamp biomicroscope, since there may not be external signs or the external signs may be so minimal that they are overlooked. The external signs of obstructive meibomian gland dysfunction may be limited to subtle alterations of the epithelium of the eyelid margins over the orifices, and pouting of the orifices of the meibomian glands with congealed material acting as obstructions. The external signs of obstructive meibomian gland dysfunction in severe to very severe instances may be obvious, and include serration and distortion of the shape of the eyelid margins. While inflammation is not usually present with mild to moderate obstructive meibomian gland dysfunction, with severe to very severe instances of obstructive meibomian gland dysfunction, inflammation may be present.
There is a correlation between the tear film lipid layer and dry eye disease. The various different medical conditions and damage to the eye and the relationship of the lipid layer to those conditions are reviewed in Sury Opthalmol 52:369-374, 2007. It is clear that the lipid layer condition has the greatest effect on dry eye disease when compared to the aqueous layer or other causes. Thus, while dry eye states have many etiologies, the inability of the meibomian gland 10 to sufficiently generate the lipid layer is a common cause of common dry eye state or MGD. MGD is a disorder where the meibomian glands 10 are obstructed or occluded. FIG. 3 illustrates an example of such obstructions or occlusions 22, 24. Plug obstructions 22 can occur in the orifice 16 of the central duct 18. Alternatively, obstructions and occlusions 22, 24 can occur that block a particular acinus 20. The obstructions or occlusions 22, 24 can mean that the meibomian glands 10 are partially blocked or plugged, completely blocked or plugged, or any variation thereof. Obstructions and occlusions 22, 24 can be in a solid, semi-solid, or thickened, congealed secretion and/or a plug, leading to a compromise, or more specifically, a decrease in or cessation of secretion. It may be appreciated from FIG. 3 that the meibomian glands 10 have a certain amount of depth. The obstructions and occlusions 22, 24 may be located at any depth below the orifice 16 of the meibomian gland 10, and may be located in the central duct 18, in one or more of the acini 20, or at a junction of the central duct 18 and the an acinus 20. Also, with a reduced or limited secretion, the meibomian gland 10 may be compromised by the occluded or obstructive condition often evidenced by a yellowish color, indicating a possible infection state. Alternatively, the meibomian gland 10 may be otherwise compromised so that the resulting protective lipid film is not adequate for preventing evaporation of the underlying layers on the eye.
MGD is frequently the result of keratotic obstructions, which partially or completely block the meibomian gland orifices 16 and/or the central duct (canal) 18 of the meibomian gland 10, or possibly the acini or acini valves (assuming they do in fact exist) or the junction of the acini 20 with the central duct 18. Such obstructions 22, 24 compromise the secretory functions of the individual meibomian glands 10. More particularly, these keratotic obstructions may be associated with or result in various combinations of bacteria, sebaceous ground substance, dead, and/or desquamated epithelial cells (see Korb et al., “Meibomian Gland Dysfunction and Contact Lens Intolerance,” Journal of the Optometric Association, Vol. 51, No. 3, (1980), pp. 243-251).
Hormonal changes, which occur during menopause and particularly changing estrogen levels, can result in thickening of the oils secreted by the meibomian glands 10. This may result in clogged meibomian gland orifices. Further, decreased estrogen levels may also enhance conditions under which staphylococcal bacteria can proliferate. This can cause migration of the bacteria into the meibomian glands 10 compromising glandular function and further contributing to occlusion, thus resulting in a decreased secretion rate of the meibomian gland 10.
When the flow of secretions from the meibomian gland 10 is restricted due to the existence of an occlusion 22, 24, cells on the eyelid margin have been observed to grow over the orifice 16. This may further restrict sebum flow and exacerbate a dry eye condition. Additional factors may also cause or exacerbate meibomian gland dysfunction including age, disorders of blinking, activities such as computer use which compromise normal blinking, contact lens use, contact lens hygiene, cosmetic use, or illness, particularly diabetes. It has been theorized that the acini 20 of the meibomian glands 10 may have valves at their junction with the main channel of the meibomian gland 10. It is theorized that if these valves exist, they may also become obstructed in some instances leading to reduced or blocked flow from the acini 20. These obstructions or occlusions 22, 24 may have various compositions.
The state of an individual meibomian gland 10 can vary from optimal, where clear meibomian fluid is produced; to mild or moderate meibomian gland dysfunction where milky fluid or inspissated or creamy secretion is produced; to total blockage, where no secretion of any sort can be obtained (see Korb et al., “Increase in Tear Film Lipid Layer Thickness Following Treatment of Meibomian Gland Dysfunction,” Lacrimal Gland, Tear Film, and Dry Eye Syndromes,” pp. 293-298, edited by D. A. Sullivan, Plenum Press, New York (1994)). Significant chemical changes of the secretions of the meibomian gland 10 occur with meibomian gland dysfunction and consequently, the composition of the naturally occurring tear film is altered, which in turn contributes to dry eye.
While the tear film operates as a singular entity and all of the layers thereof are important, the lipid layer, which is secreted from the meibomian glands, is of particular significance as it functions to slow the evaporation of the underlying layers and to lubricate the eyelid during blinking, both of which prevent dry eye and epitheliopathies.
Thus, to summarize, the meibomian glands 10 of mammalian (e.g., human) eyelids secrete oils that prevent evaporation of the tear film and provide lubrication to the eye and eyelids. These meibomian glands 10 can become blocked or plugged (occluded) by various mechanisms leading to so-called “dry eye syndrome.” While not the only cause, MGD is a known cause of dry eye syndrome. The disorder is characterized by a blockage of some sort within the meibomian glands 10 or at their surface, preventing normal lipid secretions from flowing from the meibomian glands 10 to form the lipid layer of the tear film. Such secretions serve to prevent evaporation of the aqueous tear film and lubricate the eye and eyelids 12, 14; hence, their absence can cause dry eye syndrome. Obstructions or occlusions 22, 24 of the meibomian glands 10 may be present over or at the orifice 16 of the meibomian gland 10, in the central duct 18 of the meibomian gland 10, which may be narrowed or blocked, or possibly in other locations including the passages from the acini 20 to the central duct 18.
In response to the foregoing, various treatment modalities have been developed in order to treat the dry eye condition, including drops, which are intended to replicate and replace the natural aqueous tear film and pharmaceuticals which are intended to stimulate the tear producing cells. For example, eye drops such as Refresh Endura™, Soothe™, and Systane™ brand eye drops are designed to closely replicate the naturally occurring healthy tear film. Other treatment modalities include various heating devices which are designed to assist in unclogging the meibomian glands by manual expression.
However, prior to implementing an appropriate treatment plan, the clinician must first determine whether some or all of the meibomian glands are properly secreting or are obstructed. If it is determined that the meibomian glands are obstructed, determining the degree of such obstruction is helpful in developing a treatment plan. The clinical evaluation of meibomian glands normally requires a test of their expressability. “Expressability” in this context is used to describe the ease with which secretion can be physically expelled from the meibomian gland.
MGD may be difficult to diagnose, because visible indicators are not always present. For example, meibomitis, an inflammation of the meibomian glands 10, can lead to MGD. Meibomitis may also be accompanied by blepharitis (inflammation of the eyelids). While meibomitis is obvious by inspection of the external eyelids, MGD may not be obvious even when examined with the magnification of a slit-lamp biomicroscope. This is because there may not be external signs or the external signs may be so minimal that they are overlooked. The external signs of MGD without obvious eyelid inflammation may be limited to subtle alterations of the orifices 16, overgrowth of epithelium over the orifices 16, and pouting of the orifices 16 of the meibomian glands 10 with congealed material acting as obstructions. In severe instances of MGD without obvious eyelid inflammation, the changes may be obvious, including serrated or undulated eyelid margins, orifice recession and more obvious overgrowth of epithelium over the orifices 16, and pouting of the orifices 16.
Current practice in diagnosing whether a meibomian gland is obstructed involves the application of force, usually with the thumb or finger to the external eyelid surfaces overlying the meibomian gland. The terms “gentle” and “forceful” expression have been used to describe the magnitude of the force used for meibomian gland evaluation. Further, as used herein, when referring to a “gland,” the plural is intended to be included therein and when the term “glands” is used, the singular is intended to be included as well. Observations suggest that the diagnosis of whether an individual meibomian gland is obstructed is a function of the amount of force applied to the meibomian gland. While meibomian gland disease is often painful, clinicians often apply a force to the eyelid which is greater than the minimum force required to diagnose whether or not an obstruction exists, thus inflicting unnecessary pain on the patient.